Non-invasive diagnosis of primary Sjögren's syndrome using ultrasonography and transcriptome biomarkers.

Diagnosing primary Sjögren's syndrome (pSS) is difficult due to clinical heterogeneity and the absence of non-invasive specific biomarkers. To develop non-invasive pSS diagnosis methods that integrate classic clinical indexes, major salivary gland ultrasonography (SGUS), and gene expression profiles shared by labial gland and peripheral blood, we conducted a study on a cohort of 358 subjects. We identified differentially expressed genes (DEGs) in glands and blood that were enriched in defense response to virus and type I interferon production pathways. Four upregulated DEGs common in glands and blood were identified as hub genes based on the protein-protein interaction networks. A random forest model was trained using features, including SGUS, anti-SSA/Ro60, keratoconjunctivitis sicca tests, and gene expression levels of MX1 and RSAD2. The model achieved comparable pSS diagnosis accuracy to the golden standard method based on labial gland biopsy. Our findings implicate this novel model as a promising diagnosis technique of pSS.

Performance Evaluation of Multiple Ultrasonographical Methods for the Detection of Primary Sjögren's Syndrome.

Major salivary gland ultrasonography (SGUS) is increasingly being recognized as having critical roles in differentiating primary Sjögren's syndrome (pSS) from other connective tissue disorders. Contrast-enhanced ultrasonography (CEUS) has been reported to evaluate microvascularity of lesions in different tissues with objective angiographic index, eliminating the observer-dependent defect of ultrasonography. However, there are few relevant studies concentrating on the application of CEUS in the diagnosis and assessment for pSS, and their clinical utility prospect remains uncertain. In this study, a total of 227 eligible patients were enrolled, including 161 pSS and 66 non-pSS patients with comprehensive ultrasonographic evaluation of the parotid and submandibular glands, including grayscale ultrasonography, color Doppler sonography (CDS), and CEUS. Compared with non-pSS, pSS patients had significantly higher grayscale ultrasound (US) scores and CDS blood grades in the parotid gland and significantly higher grayscale US and CEUS scores in the submandibular glands. Diagnostic model combining ultrasonographic signatures, anti-SSA/Ro60, and keratoconjunctivitis sicca (KCS) tests showed a remarkable discrimination [mean area under the curve (AUC)0.963 in submandibular glands and 0.934 in parotid glands] for pSS, and the nomogram provided excellent prediction accuracy and good calibration in individualized prediction of pSS. A combination of multiple ultrasonographical examinations of the major salivary glands (SGs) is a promising technique that may be used as a practical alternative to minor SG biopsy in the detection of pSS.

Applicability of liver stiffness measurement based nomograms to the assessments of hepatitis B related significant fibrosis and cirrhosis.

BACKGROUND: We evaluated liver fibrosis in patients with chronic hepatitis B (CHB) and mildly raised alanine transaminase (ALT) activities between 1-2 times the upper limit of normal (ULN) which was near the threshold for initiating treatment. METHODS: Nomogram-Fibrosis and Nomogram-Cirrhosis were elaborated with variables independently associated with significant fibrosis and cirrhosis determined by multivariate logistic regression. Calibration, receiver operator characteristic (ROC) and decision curves were applied to comparing nomograms with aspartate aminotransferase (AST) to platelet count (PLT) ratio index (APRI), age-AST-PLT-ALT index (FIB-4) and liver stiffness measurement (LSM). RESULTS: The Nomogram-Fibrosis was constructed with LSM, PLT, and gamma-glutamyl transpeptidase (GGT). Nomogram-Cirrhosis contained one more variable of age other than Nomogram-Fibrosis. The calibration demonstrated that the assessments of significant fibrosis or cirrhosis by nomograms were in line with liver biopsy. The AUROC of Nomogram-Fibrosis was 0.788, lager than APRI (0.586), FIB-4 (0.656) and LSM (0.735). The AUROC of Nomogram-Cirrhosis was 0.889, larger than APRI (0.642), FIB-4 (0.725) and LSM (0.837). Furthermore, the decision curve analysis suggested the most net benefits were provided by the nomograms. CONCLUSIONS: Nomogram-Fibrosis and Nomogram-Cirrhosis could be promising tools for recognizing significant fibrosis and cirrhosis for CHB patients with mild raised ALT activities.

Prediction of central compartment lymph node metastasis in papillary thyroid microcarcinoma.

OBJECTIVES: We aimed to determine the predictive factors for central compartment lymph node metastasis (LNM) in papillary thyroid microcarcinoma (PTMC). DESIGN AND PATIENTS: We undertook a retrospective study of 291 patients treated for PTMC. The following criteria were assessed to predict the presence of central compartment LNM: sex, age, tumour multifocality, tumour size, tumour bilaterality, extracapsular spread (ECS), lateral neck LNM, coexistence of chronic lymphocytic thyroiditis, BRAF(V) (600E) mutation and ultrasonography (US) features. Univariate and multivariate analyses were performed to identify clinicopathological characteristics and US findings in predicting central compartment LNM from PTMC. RESULTS: The central compartment LNM affected 133 (45.7%) of 291 patients. With use of univariate and multivariate analyses, male gender (OR 2.020; P = 0.039), tumour size (>5 mm) (OR 3.687; P = 0.015), ESC (OR 2.330; P = 0.044), lateral LNM (OR 15.075; P = 0.000) and BRAF(V) (600E) mutation (OR 2.464; P = 0.000) were independently correlated with central compartment LNM. Age, tumour multifocality, tumour bilaterality, coexistence of chronic lymphocytic thyroiditis and US characteristics were not significantly related to the presence of central compartment LNM. We have also developed a nomogram to predict the probability of central compartment LNM for an individual patient. The sensitivity was 71.9% and specificity was 70.3%, with an under the receiver operating characteristic (ROC) curve of 0.772. CONCLUSIONS: A prophylactic neck dissection of the central compartment should be considered particularly in PTMC patients with male gender, a >5 mm tumour size, ECS of the tumours, lateral LNM and positive BRAF(V) (600E) mutation.